In amyotrophic lateral sclerosis (ALS), is it difficult to catch a breath due to inspiratory muscle weakness?

Respiratory Difficulty in ALS

Yes, difficulty catching a breath is a hallmark feature of ALS due to progressive inspiratory and expiratory muscle weakness, with diaphragm involvement often preceding other motor symptoms and leading to respiratory failure as the primary cause of death. 1

Mechanism of Breathing Difficulty

Inspiratory Muscle Weakness

• Diaphragm weakness is particularly characteristic in ALS, often developing before significant limb weakness and causing acute-on-chronic hypercapnia 1
• Severe compromise of diaphragmatic function results from marked motor unit loss, leading to poor inspiratory strength, symptomatic respiratory fatigue, and progressive hypercapnia and hypoxemia—often first detected during supine sleep 2
• Patients develop a reduced respiratory reserve and may initially maintain normal CO2 levels, but any elevation in pCO2 can herald an impending respiratory crisis 1
• Minor infections like the common cold can trigger progressive hypercapnia over 24-72 hours 1

Expiratory Muscle Weakness

• Expiratory muscle weakness causes ineffective cough and poor bronchial clearance, substantially increasing the risk of respiratory infections 2
• Even mild-to-moderate expiratory muscle weakness adversely affects the expiratory pressures and flows needed for effective coughing 3
• Bulbar dysfunction further renders voluntary cough less effective 1

Compensatory Mechanisms and Dyspnea

• ALS patients with respiratory failure can exhibit respiratory-related cortical activity, reflecting cortical engagement to augment neural drive to breathe through inspiratory neck muscle recruitment 4
• This compensatory mechanism disappears during sleep (compatible with cortical contribution) and correlates with more severe dyspnea 4
• A supine Borg dyspnea score ≥3 predicts severe inspiratory muscle weakness (SNIP ≤40 cmH2O) with 80% sensitivity and 78% specificity 5

Clinical Monitoring

Key Respiratory Parameters

• Monitor forced vital capacity (FVC), sniff nasal inspiratory pressure (SNIP), maximal inspiratory/expiratory pressures (MIP/MEP), and peak cough flow (PCF) at minimum every 6 months 6
• A fall in vital capacity when supine compared to upright suggests severe diaphragm weakness 7
• Peak cough flows below 160 L/min indicate ineffective airway clearance; values below 270 L/min identify patients needing assisted cough techniques 8
• Maximal expiratory pressure below 45 cmH2O indicates absent effective coughing ability 8

Sleep and Gas Exchange

• Respiratory muscle weakness causes desaturation and hypercapnia during REM sleep before daytime symptoms appear 7
• Nocturnal hypoventilation gradually progresses to daytime hypercapnia 1

Management Approach

Non-Invasive Ventilation (NIV)

• NIV should be considered in any breathless/acutely unwell ALS patient before respiratory acidosis develops 1
• Initiate NIV based on FVC decline, MIP/MEP values, overnight oximetry, or polysomnography evidence of sleep-disordered breathing or hypoventilation 6
• Patients with bulbar impairment may not tolerate NIV or achieve adequate ventilation 6

Airway Clearance

• Teach assisted cough strategies early and employ aggressively 8
• Use mechanical insufflation-exsufflation for patients with peak cough flow <270 L/min or maximal expiratory pressure <60 cmH2O 8
• Home pulse oximetry monitors airway clearance effectiveness during respiratory illnesses 8

Advanced Respiratory Support

• For patients in whom NIV fails, who have worsening bulbar function, frequent aspiration, or declining lung function despite adequate secretion management, consider invasive mechanical ventilation via tracheostomy 6
• Mouthpiece ventilation can provide daytime ventilatory support in patients with preserved bulbar function as an adjunct to nocturnal mask NIV 6

Critical Pitfalls

• Do not wait for respiratory acidosis to develop before initiating NIV—any elevation of pCO2 may herald impending crisis 1
• Minor infections can rapidly precipitate respiratory failure in patients with already compromised respiratory reserve 1
• Respiratory muscle weakness must be profound to restrict vital capacity from inspiratory weakness alone, but even mild expiratory weakness significantly compromises cough effectiveness 3
• Patients may perform poorly on spirometry due to oro-facial muscle weakness, making non-volitional tests like phrenic nerve stimulation or SNIP particularly valuable 2